FDA Declines Approval for Oral Contrast Agent in MRI

The U.S. Food and Drug Administration (FDA) has rejected the application for a novel oral contrast agent designed to enhance MRI imaging. Ascelia Pharma, a biotechnology company based in Sweden, developed the manganese-based compound Orviglance, intended to improve visualization of focal liver lesions.

The FDA cited issues with the clinical trials supporting the agent's approval. According to the agency, the trials failed to provide convincing evidence of Orviglance's effectiveness due to shortcomings in the studies' design. Specifically, only one of three primary readers in the trial demonstrated that contrasted images were superior to non-contrasted ones. Additionally, the FDA raised concerns over potential bias from re-evaluating images without adequate justification. This reevaluation could affect new readers by exposing them to prior results.

In its formal response, the FDA recommended conducting a new controlled study with comprehensive reader training using a complete set of precontrast images. These measures aim to ensure the accuracy and impartiality of image evaluations.

Ascelia Pharma acknowledged these challenges and expressed intent to engage with the FDA for clarification, focusing on image-reading processes rather than the drug's performance. A new image evaluation method, which includes independent and blinded readers unaware of previously obtained results, has been implemented by the company. These adjustments were communicated to the FDA and incorporated into the New Drug Application.

The company plans to update on the situation following a meeting with the FDA. Ascelia emphasized its commitment to resolving the issues outlined by the FDA and advancing Orviglance's approval process.

This development is part of the FDA's broader transparency initiative, initiated in 2025, which includes public disclosure of regulatory response letters. However, this transparency endeavor faces legal challenges, with some industry stakeholders arguing that the disclosure of certain details could breach confidentiality laws.

The agency has also proposed a revision to regulations that would change the treatment of marketing applications as confidential commercial information. Such modifications could significantly impact how regulatory information is shared with the public in the future.